TABLE 1.3.

Interactions between complement and fungi in the CNS.

	Study design	Outcomes	Conclusion	References
Aspergillus spp.
1	(Human) Postmortem brain tissue specimens from subjects with cerebral aspergillosis (n16): HIV infection (n10), tumor therapy (n2), acute myeloid leukemia (n2), aplastic anemia (n1), organ transplantation (n1). Compared to non-infected control (n7).	(1) C1q, C4, C3, and C5 were upregulated in the from Aspergillus-infected brain. C1q, C4, C3, and C5 were colocalized with neurons, astrocytes, oligodendrocytes, and infiltrating macrophages. (2) High complement levels in the surrounding fibrous layer, but not in the central necrotic area loaded with fungal hyphae.	Complement synthesis increased in astrocytes, neurons, oligodendrocytes, and infiltrating macrophages in the surrounding fibrous layer.	Rambach et al., 2008
Candida spp.
1	(in vivo) Murine model of Candida albicans infection. Genetic susceptibility was assessed by intercrossing two inbred strains: A/J (C5 deficient) and C57BL/6J (B6)	(1) Fungal load in the brain, kidney, and heart was significantly different between the two inbred strains: A/J was more susceptible compared to B6. (2) C5 was a strong determinant for the brain and kidney susceptibility to infection.	C5 is a major gene responsible for genetic susceptibility to candidiasis.	Tuite et al., 2005
Cryptococcus
1	(in vivo) Cryptococcus neoformans infection model in mice (WT, C3 deficient, and C5 deficient).	(1) C3 deficiency, C5 deficiency, and C5aR blockade (specific anti-C5aR mAb) reduced the intravascular clearance of C. neoformans. (2) Upon infection, neutrophils recruitment to the lung and the brain was less efficient in C3 deficient and C5 deficient mice compared to WT. Neutrophil recruitment was also inhibited in WT mice treated with anti-C5aR. (3) C5aR deficient neutrophils failed to be recruited to the infected lung. (4) Intravascular clearance of disseminating C. neoformans is less efficient in the brain compared to the lung. (5) LPS-treatment significantly enhanced neutrophil recruitment to the brain and C. neoformans clearance.	(a) Neutrophil recruitment is essential for intravascular clearance of C. neoformans. (b) C5aR-dependent neutrophil recruitment is crucial for intravascular clearance of C. neoformans.	Sun et al., 2016

The relevant complement proteins are highlighted in bold.